2012-03-30 Brain anomalies in children exposed prenatally to a common organophosphate pesticide

Abstract

Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9–11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons.  High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right  hemisphere.

Group differences were derived from exposure effects on underlying white matter. A significant exposure × IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of  normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical  thinning, and an inverse dose–response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the                              developing human brain.

Footnotes

• ↵¹To whom correspondence should be addressed. E-mail: var1@columbia.edu.

• Author contributions: V.A.R., F.P.P., R.M.W., T.A.S., and B.S.P. designed research; M.K.H., R.B., X.H., and J.L. performed  research; D.B.B. contributed new reagents/analytic tools; R.B., X.H., and J.L. analyzed data; and V.A.R., R.B., T.A.S., and B.S.P. wrote the paper.

• Conflict of interest statement: T.A.S. has provided expert testimony on the health effects of chlorpyrifos on behalf of government entities, corporations, and/or individuals.

• This article is a PNAS Direct Submission.

• This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1203396109/-/DCSupplemental.